KRAS mutations drive adenomatoid odontogenic tumor and are independent of clinicopathological features
| Autor: | Núbia Braga Pereira, Manoela Domingues Martins, Carolina Cavaliéri Gomes, Josiane Alves França, Danyel Elias da Cruz Perez, Ricardo Luiz Cavalcanti de Albuquerque Júnior, Hélder Antônio Rebelo Pontes, Lélia Batista de Souza, Aline Carvalho Batista, Marina Gonçalves Diniz, Sílvia Ferreira de Sousa, Bruna Pizziolo Coura, Vanessa Fátima Bernardes, Ricardo Santiago Gomez |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty Adolescent MAP Kinase Signaling System Biology medicine.disease_cause Proto-Oncogene Mas Pathology and Forensic Medicine Ameloblastoma Proto-Oncogene Proteins p21(ras) Young Adult 03 medical and health sciences symbols.namesake 0302 clinical medicine Genotype-phenotype distinction medicine Humans Allele Child Sanger sequencing Adenomatoid odontogenic tumor Odontogenic tumor Oral Neoplasm Middle Aged medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Mutation symbols Female KRAS Pancreas |
| Zdroj: | Modern Pathology. 32:799-806 |
| ISSN: | 0893-3952 |
| Popis: | Adenomatoid odontogenic tumor is a benign encapsulated epithelial odontogenic tumor that shows an indolent clinical behavior. We have reported in a few adenomatoid odontogenic tumors mutations in KRAS, which is a proto-oncogene frequently mutated in cancer such as lung, pancreas, and colorectal adenocarcinomas. We aimed to assess KRAS mutations in the hotspot codons 12, 13, and 61 in a large cohort of adenomatoid odontogenic tumors and to test the association of these mutations with clinical (age, site, tumor size, follicular/extrafollicular subtypes) and histopathological parameters. Thirty eight central cases were studied. KRAS codon 12 mutations were assessed by TaqMan allele-specific qPCR (p.G12V/R) and/or Sanger sequencing, and codon 13 and 61 mutations were screened by Sanger. Histological tumor capsule thickness was evaluated by morphometric analysis. Additionally, the phosphorylated form of the MAPK downstream effector ERK1/2 was investigated. Statistical analysis was carried out to test the association of KRAS mutations with clinicopathological parameters. KRAS c.35 G >T mutation, leading to p.G12V, was detected in 15 cases. A novel mutation in adenomatoid odontogenic tumor, c.34 G >C, leading to p.G12R, was detected in 12 cases and the other 11 were wild-type. Codon 12 mutations were not associated with the clinicopathological parameters tested. RAS mutations are known to activate the MAPK pathway, and we show that adenomatoid odontogenic tumors express phosphorylated ERK1/2. In conclusion, a high proportion of adenomatoid odontogenic tumors (27/38, 71%) have KRAS codon 12 mutations, which occur independently of the clinicopathological features evaluated. Collectively, these findings indicate that KRAS mutations and MAPK pathway activation are the common features of this tumor and some cancer types. Although it is unclear why different codon 12 alleles occur in different disease contexts and the complex interactions between tumor genotype and phenotype need clarification, on the basis of our results the presence of KRAS p.G12V/R favors the adenomatoid odontogenic tumor diagnosis in challenging oral neoplasm cases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink